Gene networks associated with conditional fear in mice identified using a systems genetics approach

To uncover genetic networks governing the biology of conditional fear, we used a systems genetics approach to analyze a hybrid mouse diversity panel (HMDP) with high mapping resolution. By integrating fear phenotypes, transcript profiling data from hippocampus and striatum and genotype information, two gene co-expression networks correlated with context-dependent immobility were identified. We prioritized the key markers and genes in these pathways using intramodular connectivity measures and structural equation modeling. We mapped 27 behavioral quantitative trait loci with a false discovery rate of 5%. We also identified two gene co-expression networks correlated with context-dependent immobility. Highly connected genes in the context fear modules included Psmd6, Ube2a and Usp33, suggesting an important role for ubiquitination in learning and memory. We surveyed the architecture of brain transcript regulation and showed preservation of gene co-expression modules in hippocampus and striatum while also highlighting important differences. Rps15a, Kif3a, Stard7, 6330503K22RIK, and Plvap were among the individual genes whose transcript abundance associated strongly with fear phenotypes. Total mRNA islolated from hippocampus and striatum of strains from Hybrid Mouse Diversity Panel and gene expression quantified using Illumina MouseRef-8 v2.0 microarrays. Submission includes gene expression data from 100 strains of HMDP for hippocampus (n=1 for each strain) and 98 strains of HMDP for striatum (n=1 for each strain).